Diabetes Research and Clinical Practice - Volume 120 - Supplement 1

13-N), and the Focused Innovations Scheme of the Chinese

University of Hong Kong.

OL04-8

Identification of a mutation associated with early-onset

diabetes in the intron of INS gene with whole-exome

sequencing

Hiroto FURUTA

, Shohei MATSUNO

, Asako DOI

Shinsuke URAKI

, Hiroshi IWAKURA

, Hiroyuki ARIYASU

Hiromichi KAWASHIMA

, Masahiro NISHI

, Kishio NANJO

Takashi AKAMIZU

Wakayama Medical University,

Wakayama

Rosai Hospital, Japan

Whole-exome sequencing is a new technology for mutation

detection in genetic disorders. We explored the gene respon-

sible for a family with early-onset diabetes using this method.

In the family, the proband was diagnosed with hyperglycemia

at the age of 3 years and has been treated with insulin

immediately after diagnosed. Her two daughters were also

diagnosed with hyperglycemia at the age of 12 months and 18

months, respectively. They have been also treated with insulin

immediately after diagnosed. All exons and flanking regions of

human genome shown in the consensus coding sequence

project database were captured with specific probes (Agilent

SureSelect XT Human All Exon V4 kit) and the products were

sequenced with next generation sequencer (HiSeq2000). The

generated reads were annotated with reference sequences in

UCSC Genome Brower hg19 and two databases of variants

(dbSNP 135 and 1000 Genomes). We checked the result for

twenty-six known early-onset diabetes (MODY and/or neo-

natal diabetes) genes and a heterozygous intronic mutation

c.188-31G > A in the INS gene, which is not registered in two

databases, was identified in the genomic DNA of the proband.

The mutation was also identified in her two daughters, but not

in her son without diabetes. The substitution is located 31 bp

proximal from exon 3 in the intron 2 of the INS gene. It is

predicted to create an ectopic splice site leading to insert 29

nucleotides of intron 2 as exonic sequence in the transcript.

The abnormal insulin would induce pancreatic beta cell

apoptosis by the endoplasmic reticulum stress. This mutation

has been previously described in three reports for analyzing

the gene of neonatal diabetes. Our result suggests that the

intronic mutation c. 188-31G > A is a hot spot of causal

mutation for diabetes in the INS gene.

Treatment of Diabetes

OL05-1

Medicine-related factors that could impact on the safety and

outcomes of glucose lowering medicines (GLM) in aged care

home

Trisha DUNNING

, Sally SAVAGE

, Nicole DUGGAN

Deakin

University and Barwon Health, Australia

Background:

The McKellar Guidelines consist of 18 guidelines

and five risk assessment tools including Glucose Lowering

Medicine-related Adverse Risk Assessment and Hypogly-

caemia Risk Assessment.

Aim:

To identify medicine-related factors that could impact on

the safety and outcomes of glucose lowering medicines (GLM)

in five Victoria regional and rural aged care homes.

Method:

The study was part of a larger study to develop,

implement and evaluate the McKellar Guidelines. Data were

collected from an audit of medical records of residents with

diabetes (n = 74), researchers informally observing staff prac-

tice during visits to the care homes and interviews with

registered nurses and other care staff.

Findings:

Several issues that affect medicine safety were

identified. Blood glucose testing was not related to GLM

onset or peak action and was not regarded as important

unless the person was on insulin. GLM administration times

did not always correspond with meal times. Staff did not

realise neuroglycopaenic symptoms predominate in older

people with low blood glucose or that hypoglycaemic

unawareness is common in older people. Thus, hypogly-

caemia is often missed or mistaken for confusion or delirium.

Some GPs appeared to regard hyperglycaemia as a benign

condition.

“

Reportable blood glucose range

”

ranged from 2.5 to

25 mmol/L. No evidence was cited to support the reportable

ranges and they were not related to Guideline recommenda-

tions. Top up doses/sliding insulin scales were used tomanage

hyperglycaemia despite the fact they are contraindicated and

do not treat the underlying cause. Staff focused on adminis-

tering medicines rather than the overall process of managing

medicines and monitoring their effects.

Conclusion:

Managing medicines in aged care homes is

complicated, especially when older people with diabetes are

prescribed High Risk Medicines. Several issues were identified

that put older people at risk of medicine-related adverse

events and errors.

OL05-2

Changes in body composition during SGLT2 inhibitor

treatment and their relevance to the improvement of insulin

sensitivity

Hitomi NAKAYAMA

, Yoshie OHTSUKA

Mamiko KAWAHARA

, Yui NAKAMURA

, Shinpei IWATA

Satoko YOSHINOBU

, Rika SOGA

, Tamami OSHIGE

Seiko KAWANO

, Satomi KAKINO

, Munehisa TSURUTA

Yuji TAJIRI

, Kentaro YAMADA

Division of Endocrinology and

Metabolism, Department of Medicine, Kurume University School of

Medicine, Japan

Background and aims:

Selective sodium glucose co-trans-

porter type 2 (SGLT2) inhibitors decrease renal glucose

reabsorption, which results in reductions in plasma glucose

and body weight. Although body weight decreases soon after

the initiation of SGLT2 inhibitor therapy, it is not clear whether

the early weight loss is caused by body fat reduction or fluid

loss secondary to osmotic diuresis. Furthermore, skeletal

muscle could be reduced by the consumption of muscle

amino acids by gluconeogenesis. In this study we assessed

changes in clinical parameters and body composition together

with changes in insulin sensitivity during a week of tofogli-

flozin treatment and analyzed factors contributing to the

improvement of insulin resistance.

Materials and methods:

The subjects included 13 male and 12

female patients with type 2 diabetes. Themean agewas 47 ± 14

years with a mean BMI of 29.6 ± 6.8 kg/m

. Tofogliflozin was

administered at a dose of 20 mg/day without changing the

doses of other drugs. Insulin sensitivity was quantified by

determining the steady state plasma glucose (SSPG) concen-

tration. Body compositions were measured via multi-fre-

quency bioelectrical impedance analysis using InBody720.

iPro2 continuous glucose monitoring (CGM) devices were used

to monitor subcutaneous glucose levels

Results:

Fasting plasma glucose and 24-h average glucose

determined by CGM decreased from 175 ± 43 mg/dL to 117 ±

25 mg/dL and from 185 ± 44 mg/dL to 137 ± 29 mg/dL, respect-

ively. No hypoglycemia was detected during the study period,

and mean amplitude of glycemic excursion (MAGE) was

reduced from 97.0 ± 33.9 mg/dL to 72.7 ± 27.4 mg/dL (p = 0.01).

The subjects lost 1.7 ± 0.8 kg of body weight, and body fat mass

was reduced by 1.38 ± 1.03 kg. No significant change was

observed in muscle mass, skeletal muscle mass, or total

body water, although lower limb muscle mass was slightly but

significantly decreased. SSPG was reduced from 288 ± 81 mg/

dL to 237 ± 77 mg/dL (p = 0.0003), indicating an improvement in

insulin resistance. Changes in body fat mass and serum

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